About

Daniel Ackerman, Ph.D., is a Research Assistant Professor of Radiology at the University of Pennsylvania's Perelman School of Medicine. He is affiliated with the Department of Radiology and the Penn Image-Guided Interventions Lab. His educational background includes a B.Sc. in Human Genetics from University College London in 2006 and a Ph.D. in Genetics from University College London in 2012. Dr. Ackerman's research focuses on genetic and molecular aspects of cancer, with particular emphasis on neuroendocrine tumors and hepatocellular carcinoma. His work involves identifying structural variants in metastatic tumors, understanding the genetic drivers of cancer response to therapies, and developing novel approaches for cancer diagnosis and treatment.

Research topics

• Medicine
• Internal medicine
• Political Science
• Biology
• Genetics
• Pharmacology
• Oncology
• Computational biology
• Chemistry
• Surgery
• Radiology
• Cancer research

Selected publications

• Locoregional lactate dehydrogenase inhibition potentiates therapy and overcomes treatment resistance in hepatocellular carcinoma

  Hepatology · 2026-04-30

  article

  BACKGROUND AIMS: Metabolic inhibitors have demonstrated limited efficacy for cancer therapy due to metabolic plasticity and systemic toxicity. Locoregional therapies (LRT), such as transarterial embolization (TAE) or transarterial chemoembolization (TACE), generate ischemic stress that reprograms the tumor microenvironment (TME) toward glycolytic dependency, creating an opportunity to sensitize hepatocellular carcinoma (HCC) to metabolic inhibition. This study investigated whether pharmacologic inhibition of lactate dehydrogenase (LDH) with NCATS-SM1441 could exploit TAE-induced metabolic vulnerabilities to improve therapeutic efficacy in HCC. APPROACH RESULTS: Human HCC cell lines were exposed to replete or ischemic (TAE-like) conditions and treated with the LDH inhibitor NCATS-SM1441. Glucose/lactate flux, adenosine triphosphate (ATP) levels, and viability were assessed. In vivo, a diethylnitrosamine (DEN)-induced rat HCC model was treated with intraarterial NCATS-SM1441, TAE, or their combination. Drug distribution, tumor metabolism, necrosis, and survival were analyzed using mass spectrometry imaging, histopathology, T2-weighted magnetic resonance imaging (MRI), and survival metrics. Ischemic conditions induced LDHA expression and glycolytic flux, enhancing susceptibility to LDH inhibition. The combination of intraarterial NCATS-SM1441 before embolization increased intratumoral drug accumulation, reduced systemic exposure, and synergized with TAE to suppress lactate production, promote tumor necrosis, and significantly extend local progression-free survival. CONCLUSIONS: TAE conditions the TME to create a therapeutically targetable glycolytic dependency. Combining TAE with LDH inhibition overcomes key limitations of metabolic inhibitors as monotherapies, enhancing local control and survival with minimal systemic toxicity, supporting integration of metabolism-targeted agents with LRT for unresectable HCC.

  PublisherDOI

• Abstract No. 233 Identification of Novel Pathogenic Deletions in NET Liver Metastases with Implications for TACE Therapy

  Journal of Vascular and Interventional Radiology · 2025-02-19

  articleOpen access
  PublisherOA PDFDOI

• Optical genome mapping identifies a novel <i>PSIP1::TBL1X</i> fusion in metastatic pancreatic neuroendocrine tumors

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-19

  article1st authorCorresponding

  ABSTRACT Background and aims Effective treatment of metastatic neuroendocrine tumors (NETs) is limited by a lack of targeted therapies and clinically useful predictive biomarkers. We applied complementary genomic profiling technologies to identify genomic alterations that could lead to actionable drug targets and biomarkers. Methods Optical genome mapping (OGM) and whole exome sequencing (WES) were performed on 70 liver metastases of neuroendocrine tumors from multiple anatomical primary sites. PacBio Iso-Seq long read sequencing and western blotting was used to confirm fusion gene expression. Findings were validated by rtPCR and western blotting on a separate cohort of 17 resection specimens from 14 pancreatic NET cases. Results Somatic variant calling from OGM data detected recurrent fusions involving TBL1X ( PSIP1::TBL1X ) and BEND2 ( CHD7::BEND2 and NEO1::BEND2 ) in pancreatic neuroendocrine tumors (pNETs). BEND2 fusions were associated with high grade tumors, as previously described. The novel PSIP1::TBL1X fusion was confirmed to result in fusion transcript expression by both long-read sequencing and nested rtPCR. Presence of the PSIP1::TBL1X fusion transcript was also confirmed in a second cohort of pNET resection specimens and fusion protein expression was established by western blotting. Both TBL1X and BEND2 fusions are mutually exclusive with ATRX/DAXX mutations. Conclusion This study underscores the importance of structural variants, including fusion genes as both prognostic biomarkers and potential therapeutic targets, especially in ATRX/DAXX negative pNETs. BEND2 fusion positivity may be a clinically useful biomarker for aggressive disease. As all TBL1X fusion isoforms contain the entire TBL1X coding sequence, TBL1X inhibition could be explored as a novel treatment for TBL1X fusion positive pNETs.

  PublisherDOI

• MSI.EAGLE: An Open-Source GUI for Streamlined Mass Spectrometry Imaging Analysis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-09 · 2 citations

  preprintOpen access

  Mass Spectrometry Imaging (MSI) is an emergent tool for analyzing spatial molecular distributions, yet data complexity often hinders effective analysis. MSI.EAGLE, an open-source R-Shiny application, makes analysis accessible for non-specialists by integrating advanced tools in a user-friendly interface. The workflow leverages tools from the Cardinal MSI package, with enhanced phenotyping, segmentation, statistical analysis and visualization. The application addresses a gap in spatial biology research by empowering a broader scientific community.

  PublisherOA PDFDOI

• Hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy Distinguishes Hepatocellular Carcinoma Genetic Subgroups In Vivo.

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2025-09-16

  article

  Motivation: Aberrant activation of the CTNNB1/Wnt pathway is a common molecular alteration in Hepatocellular Carcinoma (HCC) that has been found to impact patients' response to therapy; however, there is a deficiency of non-invasive biomarkers for stratifying HCC patients based on CTNNB1 mutational status. Goal(s): We sought to identify a novel non-invasive molecular imaging biomarker of CTNNB1/Wnt pathway mutation in HCCs. Approach: We assessed metabolic flux in clinically relevant HCC patient-derived xenografts in vivo using Hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy. Results: We observed an 86% higher and 14% lower Hyperpolarized 1-13C Pyruvate conversion to Alanine and Lactate respectively in CTNNB1mutant HCCs compared to non-mutants. Impact: CTNNB1 mutant and non-mutant HCCs can be distinguished non-invasively by assessing Hyperpolarized-1-13C-Pyruvate flux to Alanine and Lactate. Our findings present a promising precision imaging strategy for patient stratification, with the potential to enhance treatment outcomes in HCC and other cancers.

  PublisherDOI

• Abstract 6852: Targeted administration of lactate dehydrogenase inhibitor during transarterial of hepatocellular cardinomas in a rat model

  Cancer Research · 2025-04-21

  article

  Abstract Introduction: Despite improvements in locoregional therapy, recurrence of hepatocellular carcinoma (HCC) remains common, as tumor cells can respond to therapy by undergoing metabolic reprogramming to utilize anaerobic glycolytic pathways via lactate dehydrogenase. In this work, we assessed the growth rates and recurrence rates of HCC in target tumors undergoing transarterial embolization (TAE) with an LDH inhibitor (LDHi), bland TAE (BLAND), and sham therapy (SHAM). Methods and Materials: Development of autochthonous HCC was induced in 25 Wistar rats using DEN and tumor progressions were tracked with serial MRI until the target tumor reached a volume of 100-300 mm3. TAE with LDHi were performed using sequential administration of 10 µg/kg LDHi followed by 40-120 µm Embosphere (Merit Medical Systems) (n=13), while bland TAE were performed using Embosphere alone(n=8). An additional cohort underwent a sham TAE procedure without the administration of Embosphere (n=4). Following surgery, rats were serially imaged using T2 MRI, where tumor growth was tracked and monitored for treatment response and potential recurrence. Rats were classified as progressive disease (PD) if there was no decrease in tumor volume by &amp;lt;20%, PR if tumor volume decreased by &amp;gt;20%, and CR if the tumor was eradicated. Recurrence following PR was classified by a &amp;gt;20% increase in tumor volume from the lowest post-treatment volume. Results: LDHi target tumors had an average %change in tumor volume of -64% from treatment volume, while the BLAND showed a -38% decrease (p=0.068). Results of a Kaplan-Meier survival analysis with a log-rank test showed a significant difference in survival between the groups (p=0.006). All SHAM rats showed no response to treatment and were classified as PD. Treatment responses in the BLAND cohort were2/8 PD and 6/8 PR, while responses in the LDHi cohort were 1/13 PD, 11/13 PR, and1/13 CR. All rats classified as PR experienced recurrence and the time of progression free survival was significantly longer in the LDHi cohort (24 days) as compared to the BLAND (13 days) (p = 0.036). Conclusion: Administration of LDHi during TAE yields a larger decrease in targeted tumor volume as compared to BLAND TAE, while also providing a statistically significant improvement in progression free survival. Citation Format: Ryan Baron, Ariful Islam, George McClung, Ryan El Ghazal, Nicholas Perkons, Alexey Gurevich, Jennifer Crainic, Daniel Ackerman, Nicolas Skuli, Gregory Nadolski, Stephen Hunt, Terence Gade. Targeted administration of lactate dehydrogenase inhibitor during transarterial of hepatocellular cardinomas in a rat model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6852.

  PublisherDOI

• Molecular Profiling Distinguishes HCC Metabotypes Identified on Hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy

  Proceedings on CD-ROM - International Society for Magnetic Resonance in Medicine. Scientific Meeting and Exhibition/Proceedings of the International Society for Magnetic Resonance in Medicine, Scientific Meeting and Exhibition · 2024-11-26

  article

  Motivation: While hyperpolarized 1-13C Pyruvate Magnetic Resonance Spectroscopy holds great promise for in vivo profiling of cellular metabolism, the molecular alterations underlying the observed metabolic phenotypes (metabotypes) remain understudied. Goal(s): We sought to characterize the molecular features contributing to the metabotypes identified on Hyperpolarized 1-13C Pyruvate MRS in hepatocellular carcinoma (HCC). Approach: We integrated transcriptomic and proteomic profiling together with hyperpolarized 1-13C Pyruvate MRS of HCC patient-derived xenografts (PDX) that recapitulate the diversity of gene and protein expression observed in patients. Results: Our data suggest that hyperpolarized 1-13C Pyruvate MRS distinguishes HCC metabotypes based on MCT4 expression. Impact: By applying clinically relevant PDX models of HCC harboring naturally occurring variability in expression of metabolic enzymes and transporters, our data provide critical insights into the interpretation of hyperpolarized 1-13C Pyruvate MRS during clinical translation.

  PublisherDOI

• Supplementary Figure Legends from HIF2α-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma

  2023-04-03

  preprintOpen access

  &lt;p&gt;Supplementary Figure Legends: Legends for all supplementary figures.&lt;/p&gt;

  PublisherOA PDFDOI

• Supplementary Tables S1 - S3 from HIF2α-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma

  2023-04-03

  supplementary-materialsOpen access

  &lt;p&gt;Supplementary Tables S1 - S3: Table S1. Expression of triglyceride synthesis genes in primary ccRCC (n=480) compared to normal kidney (n=69) samples. Table S2. Expression of cholesterol synthesis genes in primary ccRCC (n=480) compared to normal kidney (n=69) samples. Table S3. Relative concentration of acyl-carnitines in 20 primary ccRCC tumors compared to matched adjacent normal kidney samples.&lt;/p&gt;

  PublisherOA PDFDOI

• Supplementary Figures S1 - S9 from HIF2α-Dependent Lipid Storage Promotes Endoplasmic Reticulum Homeostasis in Clear-Cell Renal Cell Carcinoma

  2023-04-03

  preprintOpen access

  &lt;p&gt;Supplementary Figures S1 - S9: Supplementary Figure S1. Regulation of PLIN2 and other LD coat protein genes in ccRCC tissue. Supplementary Figure S2. PPARγ function is not required for PLIN2 expression in ccRCC. Supplementary Figure S3. HIF-2alpha dependent PLIN2 expression promotes cell viability in nutrient deprived regions of 3D tumor spheroids. Supplementary Figure S4. PLIN2 is required for lipid storage, cell viability, and maintenance of ER homeostasis in A498 cells. Supplementary Figure S5. Validation of IRE-1alpha inhibitor, PERK inhibitor, and ATF6 siRNA in A498 cells. Supplementary Figure S6. Suppression of UPR signaling in A498 cells following PLIN2 depletion. Supplementary Figure S7. Energetic effects of PLIN2 depletion in ccRCC cell lines and evidence for suppression of beta-oxidation in ccRCC tumor tissue. Supplementary Figure S8. UPR or fatty acid synthesis modulation in PLIN2 depleted cells. Supplementary Figure S9. Lipid storage protects against brefeldin A induced ER stress.&lt;/p&gt;

  PublisherDOI

Recent grants

• NIH Grant F32CA177108

  NIH · $58k · 2016

• NIH Grant F32CA17710801A1

  NIH · $55k · 2016

Frequent coauthors

• M. Celeste Simon

  39 shared

• T. Gade

  California University of Pennsylvania

  36 shared

• Nicholas R. Perkons

  23 shared

• Brian Keith

  23 shared

• Joshua D. Ochocki

  Pfizer (United States)

  22 shared

• G. Nadolski

  21 shared

• Ekaterina Bobrovnikova-Marjon

  19 shared

• Bo Li

  East China University of Science and Technology

  18 shared

Labs

• Penn Image-Guided Interventions LabPI

Education

• B.S., Human Genetics

  University College London

  2006

• Ph.D., Genetics

  University College London

  2012